Cephalosporins

Abstract

Antibacterially effective cephalosporins of the formula ##STR1## in which R 1 denotes C 1 -C 6 -alkyl, phenyl or halogen-substituted phenyl and A represents a nitrogen-containing, positively charged heterocyclic 5-membered to 7-membered ring which is bonded via N and can contain a total of up to 4 hetero-atoms from the group comprising N, O and S, and onto which up to two further rings can be fused, and which can optionally be substituted, with the proviso that, if the ring is a 6-membered ring, A does not represent an unsubstituted pyridine ring or a pyridine ring which is mono- or di-substituted by identical or different substituents from the group comprising C 1 -C 4 -alkyl, chlorine, bromine, carbamoyl or N-C 1 -C 4 -alkylcarbamoyl, or pharmaceutically acceptable salts thereof or esters thereof which can be split under physiological conditions.

We claim: 
     
       1. A compound of the formula ##STR11## in which R 1  represents C 1  -C 5  -alkyl, and A is pyrazinium or pyridazinium radical which is substituted by C 1  -6-alkyl, hydroxy-C 1  -C 4  -alkyl, carboxy C 1  -C 4  -alkyl, C 1  -C 4  -alkoxycarbony-C 1  -C 4  -alkyl, formyl-C 1  -C 4  -alkyl, C 1  -C 4  -alkylcarbonyl-C 1  -C 4  -alkyl, C 1  -C 4  -alkylcarbonyl-C 1  -C 4  -alkyl substituted by hydroxyl, carbamoyl-substituted C 1  -C 4  -alkyl, carbamoyl-substituted C 1  -C 4  -alkyl substituted on the nitrogen by hydroxyl, sulpho-C 1  -C 4  -alkyl, 1-hydroxy-1-sulphomethyl, C 1  -C 4  -alkoxy-C 1  -C 4  -alkyl, C 1  -C 4  -alkoxy-C 1  -C 4  -alkyl substituted by hydroxyl, C 1  -C 4  -alkylthio-C 1  -C 4  -alkyl, C 1  -C 4  -alkylsulphinyl-C 1  -C 4  -alkyl, C 1  -C 4  -alkylsulphonyl-C 1  -C 4  -alkyl, C 3  -alkenyloxy-C 1  -C 4  -alkyl, C 3  -alkenylthio-C 1  -C 4  -alkyl, C 3  -alkenylsulphinyl-C 1  -C 4  -alkyl, C 3  -alkenylsulphonyl-C 1  -C 4  -alkyl, cyano-C 1  -C 3  -alkyl, epoxy-C 2  -C 3  -alkyl, trifluoromethyl hydroximinomethyl, C 1  -C 3  -alkyloximinomethyl, C 3  -C 4  -alkenyl, C 3  -C 4  -alkenyl substituted by hydroxyl, C 3  -alkinyl, C 3  -C 6  -cycloalkyl, and C 3  -C 6  -cycloalkyl-methyl, C 3  -C 6  -cycloalkyl-methyl substituted on the ring by hydroxyl, by halogen, or by carboxyl, C 1  -C 4  -alkoxycarbonyl, cyano, C 5  -C 6  -cycloalkenyl, C 1  -C 4  -alkoxy, C 1  -C 4  -alkoxy substituted by hydroxyl, carboxyl or C 1  -C 4  -alkoxycarbonyl, epoxy-C 2  -C 3  -alkoxy, C 3  -alkenyloxy, C 3  -alkinyloxy, aryloxy, amino, C 1  -C 5  -alkylamino, C 1  -C 4  -dialkylamino, C 1  -C 4  -alkoxycarbonylamino, C 1  -C 4  -alkylcarbonylamino, N-C 1  -C 4  -alkyl- and dialkylcarbamoylamino, C 1  -C 4  -alkylsulphonylamino, hydroxyl, C 1  -C 4  -alkylthio, C 1  -C 4  -alkylthio substituted by hydroxyl, C 1  -C 4  -alkylsulphinyl, C 1  -C 4  -alkylsulphinyl substituted by hydroxyl, C 1  -C 4  -alkylsulphonyl, C 1  -C 4  -alkylsulphonyl substituted by hydroxyl, carboxymethylthio and C 1  -C 4  -alkoxycarbonylmethylthio, C 1  -C 4  -alkoxycarbonylmethyl-sulphinyl and -sulphonyl, C 3  -alkenylthio, C 3  -alkenylsulphinyl, C 3  -alkenylsulphonyl, phenyl, benzyl, and benzyl substituted by halogen, 2'-thienyl and 3'thienyl, formyl, C 1  -C 4  -alkylcarbonyl, C 1  -C 4  -alkylcarbonyl substituted by hydroxyl, benzoyl, C 1  -C 4  -alkylcarbonylamino, formylamino, carboxyl, C 1  -C 4  -alkoxycarbonyl, and C 1  -C 4  -alkoxycarbonyl onto which is fused a 5-membered or 6-membered ring containing up to two hetero-atoms and up to two double bonds, or a pharmaceutically acceptable salt thereof or ester thereof which can be split under physiological conditions.   
     
     
       2. A compound, salt or ester according to claim 1, in which there is a fused-on ring chosen from the group comprising cyclopenteno, dehydrocyclopenteno, cyclohexeno, dehydrocyclohexeno, benzo, furo, dihydrofuro, pyrano, dihydropyrano, thieno, dihydrothieno, thiopyrano, dihydrothiopyrano, pyrido, dihydropyrido, tetrahydropyrido, pyrimido, dihydropyrimido, tetrahydropyrimido, pyrazino, dihydropyranizo, tetrahydropyrazino pyridazino, dihydropyridazino and tetrahydropyridazino. 
     
     
       3. A compound according to claim 1, wherein such compound is 7-[1-(2-aminothiazol-4-yl)-1(Z)-propenecarboxamido]-3-pyridazinium-3-cephem-4-carboxylate, or a pharmaceutically acceptable salt thereof or ester thereof which can be split under physiological conditions. 
     
     
       4. A compound according to claim 1, wherein such compound is 7-[1-(2-aminothiazol-4-yl)-1(Z)-propenecarboxamido]-3-pyrazinium-3-cephem-4-carboxylate, or a pharmaceutically acceptable salt thereof or ester thereof which can be split under physiological conditions. 
     
     
       5. An antibacterial composition comprising an antibacterially effective amount of a compound, salt or ester according to claim 22 in admixture with a diluent. 
     
     
       6. A unit dose of a composition according to claim 5 in the form of a tablet, capsule or ampule. 
     
     
       7. A method of combating bacteria which comprises administering to a patient an antibacterially effective amount of a compound, salt or ester according to claim 1. 
     
     
       8. The method according to claim 7, wherein such compound is 7-[1-(2-aminothiazol-4-yl)-1(Z)-propenecarboxamido]-3-pyridazinium-3-cephem-4-carboxylate, or   7-[1-(2-aminothizol-4-yl)-1(Z)-propenecarboxamido]-3-pyrazinium-3-cephem-4-carboxylate, or a pharmaceutically acceptable salt thereof or ester thereof which can be split uner physiological conditions.     
     
     
       9. A compound salt or ester according to claim 2, wherein the fused-on ring is substituted by at least one of C 1  -C 4  -alkyl, C 3  -C 6  -cycloalkyl, C 1  -C 4  -alkoxy, C 1  -C 3  -hydroxyalkyl, halogen, hydroxyl, carboxyl, cyano C 1  -C 6  -alkoxycarbonyl, oxo, hydroximino, carbamoyl, sulphamoyl, amino, C 1  -C 4  -alkylamino, and C 1  -C 4  -dialkylamino.